Oxygen-Releasing Antioxidant Cryogel Scaffolds with Sustained Oxygen Delivery for Tissue Engineering Applications

With the advancement in biomaterial sciences, tissue-engineered scaffolds are developing as a promising strategy for the regeneration of damaged tissues. However, only a few of these scaffolds have been translated into clinical applications. One of the primary drawbacks of the existing scaffolds is the lack of adequate oxygen supply within the scaffolds. Oxygen-producing biomaterials have been developed as an alternate strategy but are faced with two major concerns. One is the control of the rate of oxygen generation, and the other is the production of reactive oxygen species (ROS). To address these concerns, here, we report the development of an oxygen-releasing antioxidant polymeric cryogel scaffold (PUAO-CPO) for sustained oxygen delivery. PUAO-CPO scaffold was fabricated using the cryogelation technique by the incorporation of calcium peroxide (CPO) in the antioxidant polyurethane (PUAO) scaffolds. The PUAO-CPO cryogels attenuated the ROS and showed a sustained release of oxygen over a period of 10 days. An in vitro analysis of the PUAO-CPO cryogels showed their ability to sustain H9C2 cardiomyoblast cells under hypoxic conditions, with cell viability being significantly better than the normal polyurethane (PU) scaffolds. Furthermore, in vivo studies using an ischemic flap model showed the ability of the oxygen-releasing cryogel scaffolds to prevent tissue necrosis upto 9 days. Histological examination indicated the maintenance of tissue architecture and collagen content, whereas immunostaining for proliferating cell nuclear antigen confirmed the viability of the ischemic tissue with oxygen delivery. Our study demonstrated an advanced approach for the development of oxygen-releasing biomaterials with sustained oxygen delivery as well as attenuated production of residual ROS and free radicals because of ischemia or oxygen generation. Hence, the oxygen-releasing PUAO-CPO cryogel scaffolds may be used with cell-based therapeutic approaches for the regeneration of damaged tissue, particularly with ischemic conditions such as myocardial infarction and chronic wound healing.